With a long-term career goal of designing and executing pediatric clinical drug trials focused on understanding the pharmacology of infectious disease therapies, I seek support in my career development through this Mentored Patient-Oriented Research Career Development Award (K23). With the completion of my Pediatric Infectious Diseases fellowship in June 2007, this career development plan will provide me with the necessary components for an independent physician-scientist career path at the interface between pediatric infectious diseases and pharmacology via the following: (1) formal education in pediatric pharmacology and clinical trials design, including advanced coursework in pharmacology, pharmacology seminars and journal clubs, training in the responsible conduct of research, and a Masters degree in Clinical Research at the University of California, San Diego (UCSD), (2) research training in population pharmacologic modeling, simulation, and clinical pharmacology analysis techniques at UCSD's Pediatric Pharmacology Research Unit (PPRU) and UCSD's International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group laboratory, and (3) a structured plan for publications, presentations, and mentoring oversight. This proposal is feasible because of the sound career development and research plans as well as the strong support from my mentors, advisory committee, and the Department of Pediatrics at UCSD. Despite the worldwide use of antiretrovirals in HIV-infected children, little pharmacologic data exists to determine whether the current dosing regimens are optimal. Under the guidance of Dr. Capparelli, Director of UCSD's PPRU and Dr. Spector, Director of UCSD's Mother Child Adolescent HIV Program, I will focus my research on the pharmacologic determinants that affect the pharmacokinetics and pharmacodynamics of lamivudine, zidovudine, and diagnosing in HIV-infected children. By simulating the effects of the population models developed in this proposal, we will determine whether the current dosing regimens provide optimal plasma concentrations. These data are important for the health of children worldwide as our data will provide novel, critical pharmacologic information about antiretrovirals in children and ensure that current guidelines provide optimal dosing for HIV-infected children across a wide age range. [unreadable] [unreadable] [unreadable]